This revised R01 renewal application is in response to the Program Announcement PAR-14-338, entitled Secondary Analysis of Existing Alcohol Epidemiology Data. The overall goals for this application are to assess patterns of alcohol involvement with comorbid non-alcohol substance use symptoms and disorders, specifically assessing transition patterns for these comorbid conditions, and for subgroups of the population. Although prior population-based and clinical studies have provided strong evidence for the comorbid occurrence of alcohol abuse and dependence with other substance use disorders, there has been relatively little assessment of patterns of comorbidity as users transition through different stages of involvement with alcohol and other substances. In prior decades, alcohol and tobacco were considered 'gateways', early antecedents to illegal substance use. However, recent surveillance trends indicate reduction in tobacco use, whereas marijuana use has risen, and non-medical use of prescription medications has taken a large upswing. Alcohol consumption in the past decade has also increased among adults. Given the changing attitudes and loosening of marijuana restrictions in the recent past in some areas of the US as well as greater apparent accessibility to non-medical use of prescription medications, there is a need to improve our understanding of patterns of alcohol and other drug use comorbidity. For this project renewal, we aim to assess the comorbid patterns involving alcohol and non-alcohol substances (nicotine, non-medical prescription opiod use, non- medical prescription stimulant use, and marijuana). Specifically we aim to 1) assess secular trends in alcohol comorbidity over the past 20 year period using data from the National Longitudinal Alcohol Epidemiologic Survey (NLAES) (1991-2), the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) wave 1 (2001-2), and the NESARC III (2012-3). We also aim 2) to further evaluate potential changes over time by assessing comorbid patterns of alcohol and drug involvement prospectively with latent class (LCA) and latent transition analysis (LTA) using the 3-year prospective data from the NESARC waves 1 and 2, and the National Comorbidity Survey (NCS) and its 10-year follow-up. 3) Based on concepts in problem behavior theory, we will also assess potential predictors of progression through stages of alcohol and drug involvement, as well as protective factors and those associated with recovery from more severe stages of comorbid alcohol and drug use. Our proposed analyses will examine comorbid patterns by sex, race-ethnicity and for the adolescence/young adulthood subgroups. 4) We aim to incorporate advanced statistical strategies in our analyses, and use propensity score methods with LTA models to improve our ability to draw causal inferences from the observational data. Alcohol and other drug use comorbidity is highly prevalent, and findings from the proposed project analyses should increase our understanding of these important comorbid associations and improve our ability to identify potential targets for prevention and early intervention.